IUPHAR-review: The integration of classic psychedelics into current substance use disorder treatment models.

Substance use disorders (SUDs) have an enormous impact on public health. With classic psychedelic-assisted therapies showing initial promise in treating multiple SUDs, it is possible that these treatments will become legally available options for patients with SUDs in the future. This article highlights how classic psychedelic-assisted therapies might be integrated into current clinical practice. We first describe contemporary evidence-based treatments for SUDs and highlight how classic psychedelic-assisted therapies might fit within each treatment. We suggest that classic psychedelic-assisted therapies can be integrated into most mainstream evidence-based SUD treatments that are currently used in clinical settings, indicating broad compatibility of classic psychedelics with contemporary SUD treatment paradigms.

Validation of the Sexual Discounting Task for Use in Adolescents.

The Sexual Discounting Task (SDT) was developed to evaluate the effects of delay on decision making as it relates to sexual risk-taking behaviors. Though previously validated with other populations, including urban emerging adults, the current study sought to validate the SDT with adolescents. A sample of adolescents (N = 155; 61% female) between ages 14 and 21 (Mage = 19.5 years) was recruited to complete the SDT (involving choices between immediate unprotected sex and delayed sex with a condom with hypothetical sexual partners) and the Delay Discounting Task (a delay discounting task for money outcomes). Additionally, they completed several self-report measures assessing demographics, sexual behavior, and sexual history. If the condom was readily available, respondents were more likely to use a condom for partners who were judged "most likely to have an STI" and for those that participants were "least likely to have sex with." Moreover, when a condom was not immediately available, greater self-reported sexual risk-taking was related to greater sexual discounting (i.e., greater effects of delay on decreasing condom use). Furthermore, sexual discounting was greater among partners deemed more desirable and those judged "least likely to have an STI." Differences in sexual discounting were significant after controlling for immediately available condom use. Findings from the current study suggest that the SDT is clinically meaningful for adolescents and is sensitive to factors that influence real-world decisions to use condoms. Future treatment and prevention should consider delay discounting as an important variable affecting sexual risk behavior.

E-cigarette Price Impacts legal and Black-Market Cigarette Purchasing Under a Hypothetical Reduced-Nicotine Cigarette Standard.

INTRODUCTION: The Tobacco Control Act gives the U.S. Food and Drug Administration authority to establish a reduced-nicotine content standard in combusted cigarettes. This future potential regulation may pose a significant public health benefit; however, black markets may arise to meet demand for normal-nicotine content cigarettes among smokers unwilling to transition to or use an alternative product. AIMS AND METHODS: We determined the behavioral-economic substitutability of illicit normal-nicotine content cigarettes and e-cigarettes for reduced-nicotine content cigarettes in a hypothetical reduced-nicotine regulatory market. Adult cigarette smokers were recruited online to complete hypothetical cigarette purchasing tasks for usual-brand cigarettes, reduced-nicotine content cigarettes, and illicit normal-nicotine content cigarettes, as well as a cross-commodity task in which reduced-nicotine content cigarettes were available across multiple prices and illicit cigarettes were concurrently available for $12/pack. Participants completed two three-item cross-commodity purchasing tasks in which e-cigarettes were available for $4/pod or $12/pod alongside reduced-nicotine content cigarettes and illicit cigarettes. RESULTS: Usual-brand cigarette purchasing was greater than illicit normal-nicotine content cigarettes and less than reduced-nicotine content cigarettes. In the cross-commodity purchasing tasks, illicit cigarettes and e-cigarettes both served as economic substitutes for reduced-nicotine content cigarettes; however, when e-cigarettes were available for $4/pod, they were purchased at greater levels than illicit cigarettes and resulted in greater reductions in reduced-nicotine content cigarettes purchasing than when available for $12/pod. CONCLUSIONS: These data suggest that some smokers are willing to engage in illicit cigarette purchasing in a reduced-nicotine regulatory environment, but e-cigarette availability at lower prices may reduce black-market engagement and shift behavior away from combusted cigarette use. IMPLICATIONS: E-cigarettes available at low, but not high, prices were stronger substitutes for legal, reduced-nicotine content cigarettes than illegal, normal-nicotine content cigarettes in a hypothetical reduced-nicotine tobacco market. Our findings suggest the availability of relatively inexpensive e-cigarettes may reduce illicit cigarette purchasing and combusted cigarette use under a reduced-nicotine cigarette standard.

Delay Discounting and Sexual Decision-Making: Understanding Condom Use Behavior Among U.S. College Students.

Condoms provide protection against sexually transmitted diseases; however, condomless sex remains common among college students and intentions to use condoms do not consistently translate into condom use. This study tested which indicator of condom use intentions from a delay discounting paradigm of condom-protected sex best accounted for variance in condom use behavior. The sample consisted of 187 sexually active college students (51.9% female) who completed measures of condom use during vaginal and anal sex over the past three months and a decision-making paradigm regarding condom intentions with hypothetical sexual partners. In separate models, condom behavior was regressed on one of three indicators of condom intentions: initial intentions to use a condom, delay discounting of condom-protected sex, and overall area under the curve across all trials. Results showed that delay discounting of condom-protected sex best accounted for variance in absolute frequency of condomless sex, whereas initial intentions to use a condom best accounted for variance in relative proportion of condomless sex. Future research directions and implications for interventions are discussed.

Psychedelics and Consciousness: Distinctions, Demarcations, and Opportunities.

Psychedelic substances produce unusual and compelling changes in conscious experience that have prompted some to propose that psychedelics may provide unique insights explaining the nature of consciousness. At present, psychedelics, like other current scientific tools and methods, seem unlikely to provide information relevant to the so-called "hard problem of consciousness," which involves explaining how first-person experience can emerge. However, psychedelics bear on multiple "easy problems of consciousness," which involve relations between subjectivity, brain function, and behavior. In this review, we discuss common meanings of the term "consciousness" when used with regard to psychedelics and consider some models of the effects of psychedelics on the brain that have also been associated with explanatory claims about consciousness. We conclude by calling for epistemic humility regarding the potential for psychedelic research to aid in explaining the hard problem of consciousness while pointing to ways in which psychedelics may advance the study of many specific aspects of consciousness.

Attention-Deficit/Hyperactivity Disorder Symptoms Are Associated with Greater Delay Discounting of Condom-Protected Sex and Money.

Attention-deficit/hyperactivity disorder (ADHD) is associated with increased risk of detrimental life outcomes. Recent research also indicates that ADHD is associated with sexual risk behavior, such as unprotected sex. Some risky sexual behaviors may be driven, in part, by preference for immediate rewards, referred to as delay discounting, which is prominent in etiological models of ADHD. Therefore, the present study examined the effect of delay on preference for both monetary and sexual outcomes in adults with many ADHD symptoms (both on and off medication) and with fewer ADHD symptoms. Online participants (N = 275; n = 161 males, n = 114 females) completed a monetary delay discounting task, assessing preference for smaller sooner versus larger delayed hypothetical money, and the Sexual Delay Discounting Task, assessing preference for condom use in hypothetical casual sex scenarios based on delay until condom availability. Those with greater ADHD symptoms discounted delayed monetary outcomes as well as delayed condom-protected sex (i.e., preferred sooner money rewards and immediate unprotected sex) significantly more than those with fewer symptoms; however, no effect of current medication use was found across monetary or sexual delay discounting among those with greater ADHD symptoms. This study is the first to demonstrate the relation between ADHD symptoms and reduced condom-use likelihood. Increased discounting of delayed condom-protected sex might constitute one mechanism of risky sexual behavior among individuals with ADHD symptoms. Interventions geared toward increasing condom use in situations in which condoms may otherwise be unavailable, may mitigate risky sexual behaviors and their associated harms in this population.

Psychedelics and Psychotherapy.

Psychedelics have shown great promise in modern clinical trials for treating various psychiatric conditions. As a transdiagnostic treatment that exerts its effects through subjective experiences that leave enduring effects, it is akin to psychotherapy. To date, there has been insufficient discussion of how psychedelic therapy is similar to and different from conventional psychotherapy. In this article, we review the shared features of effective conventional psychotherapies and situate therapeutic psychedelic effects within those. We then discuss how psychedelic drug effects might amplify conventional psychotherapeutic processes-particularly via effects on meaning and relationship-as well as features that make psychedelic treatment unique. Taking into account shared features of conventional psychotherapies and unique psychedelic drug effects, we create a framework for understanding why psychedelics are likely to be effective with very diverse types of psychotherapies. We also review the formal psychotherapies that have been adjunctively included in modern psychedelic trials and extend the understanding of psychedelics as psychotherapy towards implications for clinical ethics and trial design. We aim to provide some common conceptual vocabulary that can be used to frame therapeutic psychedelic effects beyond the confines of any one specific modality.

Predicting changes in substance use following psychedelic experiences: natural language processing of psychedelic session narratives.

Background: Experiences with psychedelic drugs, such as psilocybin or lysergic acid diethylamide (LSD), are sometimes followed by changes in patterns of tobacco, opioid, and alcohol consumption. But, the specific characteristics of psychedelic experiences that lead to changes in drug consumption are unknown.Objective: Determine whether quantitative descriptions of psychedelic experiences derived using Natural Language Processing (NLP) would allow us to predict who would quit or reduce using drugs following a psychedelic experience.Methods: We recruited 1141 individuals (247 female, 894 male) from online social media platforms who reported quitting or reducing using alcohol, cannabis, opioids, or stimulants following a psychedelic experience to provide a verbal narrative of the psychedelic experience they attributed as leading to their reduction in drug use. We used NLP to derive topic models that quantitatively described each participant's psychedelic experience narrative. We then used the vector descriptions of each participant's psychedelic experience narrative as input into three different supervised machine learning algorithms to predict long-term drug reduction outcomes.Results: We found that the topic models derived through NLP led to quantitative descriptions of participant narratives that differed across participants when grouped by the drug class quit as well as the long-term quit/reduction outcomes. Additionally, all three machine learning algorithms led to similar prediction accuracy (~65%, CI = ±0.21%) for long-term quit/reduction outcomes.Conclusions: Using machine learning to analyze written reports of psychedelic experiences may allow for accurate prediction of quit outcomes and what drug is quit or reduced within psychedelic therapy.

Microenterprise Intervention to Reduce Sexual Risk Behaviors and Increase Employment and HIV Preventive Practices Among Economically-Vulnerable African-American Young Adults (EMERGE): A Feasibility Randomized Clinical Trial.

Economic vulnerability, such as homelessness and unemployment, contributes to HIV risk among U.S. racial minorities. Yet, few economic-strengthening interventions have been adapted for HIV prevention in this population. This study assessed the feasibility of conducting a randomized clinical trial of a 20-week microenterprise intervention for economically-vulnerable African-American young adults. Engaging MicroenterprisE for Resource Generation and Health Empowerment (EMERGE) aimed to reduce sexual risk behaviors and increase employment and uptake of HIV preventive behaviors. The experimental group received text messages on job openings plus educational sessions, mentoring, a start-up grant, and business and HIV prevention text messages. The comparison group received text messages on job openings only. Primary feasibility objectives assessed recruitment, randomization, participation, and retention. Secondary objectives examined employment, sexual risk behaviors, and HIV preventive behaviors. Outcome assessments used an in-person pre- and post-intervention interview and a weekly text message survey. Several progression criteria for a definitive trial were met. Thirty-eight participants were randomized to experimental (n = 19) or comparison group (n = 19) of which 95% were retained. The comparison intervention enhanced willingness to be randomized and reduced non-participation. Mean age of participants was 21.0 years; 35% were male; 81% were unemployed. Fifty-eight percent (58%) of experimental participants completed ≥ 70% of intervention activities, and 74% completed ≥ 50% of intervention activities. Participation in intervention activities and outcome assessments was highest in the first half (~ 10 weeks) of the study. Seventy-one percent (71%) of weekly text message surveys received a response through week 14, but responsiveness declined to 37% of participants responding to ≥ 70% of weekly text message surveys at the end of the study. The experimental group reported higher employment (from 32% at baseline to 83% at week 26) and lower unprotected sex (79% to 58%) over time compared to reported changes in employment (37% to 47%) and unprotected sex (63% to 53%) over time in the comparison group. Conducting this feasibility trial was a critical step in the process of designing and testing a behavioral intervention. Development of a fully-powered effectiveness trial should take into account lessons learned regarding intervention duration, screening, and measurement.Trial Registration ClinicalTrials.gov. NCT03766165. Registered 04 December 2018. https://clinicaltrials.gov/ct2/show/NCT03766165.

The Hotel Room Purchase Task: Effects of Gender and Partner Desirability on Demand for Hypothetical Sex in Individuals with Disordered Cocaine Use and Controls.

Hypothetical purchase tasks allow for rapid assessment of behavioral economic demand for numerous commodities and are useful in evaluating reinforcer pathologies, such as substance and behavioral addiction. Currently, there is not a task for evaluating demand for sex without requiring implicit engagement in sex work. The current study used a novel purchase task with hotel rooms for sex as the hypothetical commodity to assess demand for sex in individuals with disordered cocaine use, a population that frequently engages in risky sexual behavior. Adults meeting criteria for cocaine abuse or dependence (13 males, ten females) and noncocaine-using controls (eight males, three females) chose hypothetical sexual partners from a series of photographs and endorsed two partners with whom they would most and least like to have sex. Participants then completed the hotel purchase task for both partners, wherein they reported how many nights at a hotel room, at prices from $10 to $1280 per night, they would purchase in a year. Demand intensity was significantly greater and demand elasticity was significantly lower for the most preferred relative to the less preferred partner. Males demonstrated significantly greater intensity and lesser elasticity for sex than females. Demand metrics did not differ between the cocaine and control group. This task may serve as a useful measure of demand for sex without requiring implicit hypothetical engagement in sex work. Future studies exploring the relation between task performance and other characteristics such as sexual dysfunction, in addition to acute substance administration effects, may further determine the task's clinical utility.

Sexual Probability Discounting: A Mechanism for Sexually Transmitted Infection Among Undergraduate Students.

Lack of condom use among youth is a major contributor to the spread of sexually transmitted infections (STIs) including HIV/AIDS, which has lifelong deleterious health consequences. College students (N = 262) completed the Sexual Probability Discounting Task in which participants reported their likelihood of condom use under various probabilities of contracting an STI. Each participant completed the task in regard to different STIs including HIV/AIDS and different partners. Results showed that the likelihood of condom-protected sex generally decreased as HIV/AIDS and other STI contraction became less probable. Moreover, condom-protected sex likelihood was related to STI type (e.g., decreased condom-protected sex in chlamydia relative to HIV/AIDS condition) and partner desirability (decreased condom-protected sex with more desirable partners). Results are the first to show that compared to other STIs, HIV/AIDS had the most influence on condom-protected sex. Results showed probability discounting contributed to lack of condom-protected sex and offers a novel framework for examining determinants of within-subject variability in condom use.

Perceived risk of developing smoking-related disease among persons living with HIV.

Perceived risk of smoking is associated with smoking status, interest in quitting, cessation attempts, and quit success. Research is needed to explore risk perceptions of developing smoking-related disease among persons living with HIV (PLWH). Data came from 267 HIV-positive smokers who completed an online survey assessing perceived health risks associated with (a) generic smoking status; (b) generic non-smoking status; (c) their own personal current smoking; and (d) a hypothetical situation in which they were a non-smoker. PLWH perceived greater risk associated with their current smoking versus hypothetical personal non-smoking (p's < 0.001), and greater risks associated with generic smoking status compared with their current smoking (p's < 0.001). Being on HIV medication (ß = 0.65, 95% CI = 0.17, 1.12), interest in quitting smoking (ß = 0.89, 95% CI = 0.45, 1.32), and having an HIV healthcare provider who has recommended cessation (ß = 1.04, 95% CI = 0.42, 1.67) were positively associated with perceived risk of developing smoking-related diseases. Findings have implications for developing targeted interventions to correct misperceptions regarding the health risks of smoking among PLWH, a population at particular risk for smoking and smoking-related morbidity and mortality.

Working Memory Training for Adolescents With Cannabis Use Disorders: A Randomized Controlled Trial.

Adolescent cannabis use is associated with working memory impairment. The present randomized controlled trial assigned adolescents ages 14 to 21 enrolled in cannabis use treatment to receive either working memory training (experimental group) or a control training (control group) as an adjunctive treatment. Cognitive function, drug use, and other outcomes were assessed before and after training. We observed few differences in cognitive, functional, or self-reported drug use outcomes as a function of training group, although tetrahydrocannabinol (THC) urinalysis results favored the experimental group. These findings are similar to previous studies in substance users, which have shown limited transfer effects for working memory training.

Positive smoking cessation-related interactions with HIV care providers increase the likelihood of interest in cessation among HIV-positive cigarette smokers.

Smoking cessation has proven to be a challenge for HIV-positive smokers. Patient and provider characteristics may provide barriers to smoking cessation. We aimed to identify characteristics associated with interest in cessation as well as characterize use of, current interest in, and provider recommendations for smoking cessation modalities. Data came from 275 HIV-positive smokers recruited online. Half (49.1%) of the sample was interested in quitting; daily smoking was associated with decreased likelihood of interest in cessation, whereas making a lifetime quit attempt, receiving encouragement to quit from an HIV care provider, and greater frequency of discussions regarding cessation with HIV care providers were associated with increased likelihood of interest in cessation. Nicotine replacement therapy was the most commonly used (42.9%), generated the most interest (59.1%), and was the most commonly clinician-recommended (70.7%) cessation modality. Findings emphasize the importance of the healthcare provider-patient relationship for smoking cessation promotion in HIV-positive smokers.

Discounting of Condom-Protected Sex as a Measure of High Risk for Sexually Transmitted Infection Among College Students.

The study examined sexual delay discounting, or the devaluation of condom-protected sex in the face of delay, as a risk factor for sexually transmitted infection (STI) among college students. Participants (143 females, 117 males) completed the sexual delay discounting task (Johnson & Bruner, 2012) and questionnaires of risky sexual behavior, risk perception, and knowledge. Participants exhibited steeper sexual delay discounting (above and beyond general likelihood of having unprotected sex) when partners were viewed as more desirable or less likely to have a STI, with males demonstrating greater sexual delay discounting than females across most conditions. Importantly, greater self-reported risky sexual behaviors were associated with higher rates of sexual delay discounting, but not with likelihood of using a condom in the absence of delay. These results provide support for considering sexual delay discounting, with particular emphasis on potential delays to condom use, as a risk factor for STI among college students.

Long-term follow-up of psilocybin-facilitated smoking cessation.

BACKGROUND: A recent open-label pilot study (N = 15) found that two to three moderate to high doses (20 and 30 mg/70 kg) of the serotonin 2A receptor agonist, psilocybin, in combination with cognitive behavioral therapy (CBT) for smoking cessation, resulted in substantially higher 6-month smoking abstinence rates than are typically observed with other medications or CBT alone. OBJECTIVES: To assess long-term effects of a psilocybin-facilitated smoking cessation program at ≥12 months after psilocybin administration. METHODS: The present report describes biologically verified smoking abstinence outcomes of the previous pilot study at ≥12 months, and related data on subjective effects of psilocybin. RESULTS: All 15 participants completed a 12-month follow-up, and 12 (80%) returned for a long-term (≥16 months) follow-up, with a mean interval of 30 months (range = 16-57 months) between target-quit date (i.e., first psilocybin session) and long-term follow-up. At 12-month follow-up, 10 participants (67%) were confirmed as smoking abstinent. At long-term follow-up, nine participants (60%) were confirmed as smoking abstinent. At 12-month follow-up 13 participants (86.7%) rated their psilocybin experiences among the five most personally meaningful and spiritually significant experiences of their lives. CONCLUSION: These results suggest that in the context of a structured treatment program, psilocybin holds considerable promise in promoting long-term smoking abstinence. The present study adds to recent and historical evidence suggesting high success rates when using classic psychedelics in the treatment of addiction. Further research investigating psilocybin-facilitated treatment of substance use disorders is warranted.

Neuroticism is associated with challenging experiences with psilocybin mushrooms.

OBJECTIVES: Classic hallucinogens (e.g. psilocybin and LSD) have substantial effects on perception, cognition, and emotion that can often be psychologically challenging, however we know very little regarding the source of significant individual variability that has been observed in the frequency and intensity of challenging experiences (i.e. "bad trips") with psychedelics. Previous clinical and observational literature suggests that there may be an association between neuroticism and challenging psychedelic experiences. METHODS: Data from two online surveys of challenging experiences with psilocybin were analyzed. Multivariate analysis was used to estimate the associations between total score and scores from seven sub-factors (fear, grief, physical distress, insanity, isolation, death, and paranoia) of the Challenging Experience Questionnaire (CEQ), and scale scores from the Ten Item Personality Inventory (TIPI) in Study 1 (N=1993) and the Big Five Inventory (BFI) in Study 2 (N = 981). RESULTS: CEQ scores were negatively associated with emotional stability scores (the inverse of neuroticism) in Study 1 and positively associated with neuroticism scores in Study 2. CONCLUSIONS: Neuroticism may contribute to the strength of challenging experiences in uncontrolled settings.

Naltrexone but Not Ketanserin Antagonizes the Subjective, Cardiovascular, and Neuroendocrine Effects of Salvinorin-A in Humans.

BACKGROUND: Salvinorin-A is a terpene found in the leaves of the plant Salvia divinorum. When administered to humans, salvinorin-A induces an intense but short-lasting modified state of awareness, sharing features with those induced by the classical serotonin-2A receptor agonist psychedelics. However, unlike substances such as psilocybin or mescaline, salvinorin-A shows agonist activity at the kappa-opioid receptor rather than at the serotonin-2A receptor. Here, we assessed the involvement of kappa-opioid receptor and serotonin-2A agonism in the subjective, cardiovascular, and neuroendocrine effects of salvinorin-A in humans. METHODS: We conducted a placebo-controlled, randomized, double-blind study with 2 groups of 12 healthy volunteers with experience with psychedelic drugs. There were 4 experimental sessions. In group 1, participants received the following treatment combinations: placebo+placebo, placebo+salvinorin-A, naltrexone+placebo, and naltrexone+salvinorin-A. Naltrexone, a nonspecific opioid receptor antagonist, was administered at a dose of 50mg orally. In group 2, participants received the treatment combinations: placebo+placebo, placebo+salvinorin-A, ketanserin+placebo, and ketanserin+salvinorin-A. Ketanserin, a selective serotonin-2A antagonist, was administered at a dose of 40mg orally. RESULTS: Inhalation of 1mg of vaporized salvinorin-A led to maximum plasma concentrations at 1 and 2 minutes after dosing. When administered alone, salvinorin-A severely reduced external sensory perception and induced intense visual and auditory modifications, increased systolic blood pressure, and cortisol and prolactin release. These effects were effectively blocked by naltrexone, but not by ketanserin. CONCLUSIONS: Results support kappa opioid receptor agonism as the mechanism of action underlying the subjective and physiological effects of salvinorin-A in humans and rule out the involvement of a serotonin-2A-mediated mechanism.

Alcohol Increases Delay and Probability Discounting of Condom-Protected Sex: A Novel Vector for Alcohol-Related HIV Transmission.

BACKGROUND: Alcohol use, especially at binge levels, is associated with sexual HIV risk behavior, but the mechanisms through which alcohol increases sexual risk taking are not well-examined. Delay discounting, that is, devaluation of future consequences as a function of delay to their occurrence, has been implicated in a variety of problem behaviors, including risky sexual behavior. Probability discounting is studied with a similar framework as delay discounting, but is a distinct process in which a consequence is devalued because it is uncertain or probabilistic. METHODS: Twenty-three, nondependent alcohol users (13 male, 10 female; mean age = 25.3 years old) orally consumed alcohol (1 g/kg) or placebo in 2 separate experimental sessions. During sessions, participants completed tasks examining delay and probability discounting of hypothetical condom-protected sex (Sexual Delay Discounting Task, Sexual Probability Discounting Task) and of hypothetical and real money. RESULTS: Alcohol decreased the likelihood that participants would wait to have condom-protected sex versus having immediate, unprotected sex. Alcohol also decreased the likelihood that participants would use an immediately available condom given a specified level of sexually transmitted infection (STI) risk. Alcohol did not affect delay discounting of money, but it did increase participants' preferences for larger, probabilistic monetary rewards over smaller, certain rewards. CONCLUSIONS: Acute, binge-level alcohol intoxication may increase sexual HIV risk by decreasing willingness to delay sex in order to acquire a condom in situations where one is not immediately available, and by decreasing sensitivity to perceived risk of STI contraction. These findings suggest that delay and probability discounting are critical, but heretofore unrecognized, processes that may mediate the relations between alcohol use and HIV risk.

Salvinorin-A Induces Intense Dissociative Effects, Blocking External Sensory Perception and Modulating Interoception and Sense of Body Ownership in Humans.

BACKGROUND: Salvinorin-A is a terpene with agonist properties at the kappa-opioid receptor, the binding site of endogenous dynorphins. Salvinorin-A is found in Salvia divinorum, a psychoactive plant traditionally used by the Mazatec people of Oaxaca, Mexico, for medicinal and spiritual purposes. Previous studies with the plant and salvinorin-A have reported psychedelic-like changes in perception, but also unusual changes in body awareness and detachment from external reality. Here we comprehensively studied the profiles of subjective effects of increasing doses of salvinorin-A in healthy volunteers, with a special emphasis on interoception. METHODS: A placebo and three increasing doses of vaporized salvinorin-A (0.25, 0.50, and 1mg) were administered to eight healthy volunteers with previous experience in the use of psychedelics. Drug effects were assessed using a battery of questionnaires that included, among others, the Hallucinogen Rating Scale, the Altered States of Consciousness, and a new instrument that evaluates different aspects of body awareness: the Multidimensional Assessment for Interoceptive Awareness. RESULTS: Salvinorin-A led to a disconnection from external reality, induced elaborate visions and auditory phenomena, and modified interoception. The lower doses increased somatic sensations, but the highest dose led to a sense of a complete loss of contact with the body. CONCLUSIONS: Salvinorin-A induced intense psychotropic effects characterized by a dose-dependent gating of external audio-visual information and an inverted-U dose-response effect on body awareness. These results suggest a prominent role for the kappa opioid receptor in the regulation of sensory perception, interoception, and the sense of body ownership in humans.